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Keywords:

  • Notch1;
  • colon cancer;
  • proliferation;
  • cell cycle;
  • apoptosis;
  • cancer stem cells

Abstract

BACKGROUND:

The aberrant activation of the Notch signaling has been associated with the development of colon cancers. However, the role of Notch1 in the pathogenesis of colon cancers is poorly understood.

METHODS:

The expression of Notch1 in colon cancer tissues and nontumor tissues and in colon cancer cell lines was examined by Western blot analysis and immunohistochemistry. The impact of small interfering RNA (siRNA)-mediated Notch1 knockdown or Notch1 intracellular domain (NICD)-based transgene-induced Notch1 overexpression on the proliferation, cell cycling, apoptosis, colony formation, and tumorsphere formation in vitro and the development and growth of implanted tumors in vivo was characterized.

RESULTS:

Notch1 was overexpressed in colon cancer tissues, and the levels of Notch1 expression in different types of colon cancers were associated with the pathologic grade, progression, and metastasis of colon cancers. Furthermore, knockdown of Notch1 significantly inhibited the proliferation, colony formation, and tumorsphere formation of SW480 and HT-29 cells, induced apoptosis and cell cycle arrest at G0/G1 phase, and mitigated the development and growth of implanted colon cancers in vivo. In contrast, Notch1 overexpression promoted the proliferation, colony formation, cell cycling, and tumorsphere formation of colon cancer cells in vitro and the development and growth of implanted colon cancers in vivo, but it inhibited spontaneous apoptosis.

CONCLUSIONS:

The current results indicated that Notch1 signaling positively regulates the growth of colon cancers. Conceivably, the modulation of Notch1-related signaling may be a promising therapy for human colon cancers. Cancer 2010. © 2010 American Cancer Society.